We have recently developed biochemical selection systems for seven of the essential amino acids that are required for the growth of mammalian cells. It has been documented since the 1950's that the alpha-keto acids of the essential amino acids can substitute for the essential amino acids in rat nutritional experiments. Several aminotransferases have been described in mammalian systems that are responsible for the conversion of alpha-keto acids to the essential amino acids. Therefore, genes exist in the mammalian genome that permit the growth of the entire organism when starved for a given essential amino acid (if the appropriate alpha-keto acid is provided). The basis of our in vitro biochemical selection system stems from the in vivo observations described above. The principle of these selection systems is the following: If a cultured cell expresses a specific aminotransferase, it can convert an alpha-keto acid of an essential amino acid into the appropriate essential amino acid and, hence, live. We have identified 12 compounds that can replace the essential amino acid requirement of cultured mammalian cells. These selection procedures permit one to isolate a new class of auxotrophic mutants in mammalian cells and, potentially, could be used in selecting for or against differentiated cell types in culture. We propose to study the genetic control of the enzymes involved in these selection procedures by somatic cell hybridization. Genetic mapping of several aminotransferases will be carried out using the mouse x human hybrid. With the aid of biochemical selection systems involving the essential amino acids, we propose to develop methods for the prenatal diagnosis of the iminopeptiduria, prolidase deficiency, and other aminoacidurias.